HERG channel

from Wikipedia, the free encyclopedia

The hERG channel (abbreviation for h uman E ther-a-go-go R elated G ene) is a voltage-activated , externally rectifying potassium channel in cardiac muscle cells and nerve cells of the subthalamic nucleus .

properties

The channel consists of four subunits with six transmembrane domains each and is responsible for the partial repolarization through a rapid outflow of potassium I Kr during the action potential in the heart. The hERG channel has an influence on cell division and apoptosis .

structure

The KCNH2 protein

The hERG potassium channels can either be homo- or heterotetramers of α-subunits or heterotetramers of α- and β-subunits. The proteins Kv11.1 ( gene : KCNH2 ), Kv11.2 ( KCNH6 ), Kv11.3 ( KCNH7 ) or Kv7.1 ( KCNQ1 ), and MinK ( KCNE1 ), MiRP1 ( KCNE2 ) and MiRP2 can function as the α unit ( KCNE3 ) are possible β-units. Not all combinations are allowed.

Pathophysiology

Changes in the channel lead to long or short QT syndrome . Since the repolarization of the action potential is changed, dangerous cardiac arrhythmias can occur. After some pharmaceuticals have inadvertently influenced the HERG channel, the American regulatory authority stipulates that all new active ingredients are tested for their HERG activity. The tremendous need for these tests was one of the main driving forces behind the development of automated ion channel analysis .

Naming

The gene coding for the protein is located in locus Chr.7 q35-q36, ie on the q arm of human chromosome 7 in sections 35 and 36. The gene is related to the Ether-A-Go-Go gene found in Drosophila . Mutations in this gene cause the affected flies to twitch their feet under ether anesthesia, reminiscent of the famous dances from the then legendary rock club Whiskey A Go-Go . The name was given by William D. Kaplan in the 1960s.

Web links

Individual evidence

  1. ↑ JI Vandenberg, MD Perry, MJ Perrin, SA Mann, Y. Ke, AP Hill: hERG K (+) channels: structure, function, and clinical significance. In: Physiological Reviews . Volume 92, Number 3, July 2012, pp. 1393-1478, ISSN  1522-1210 . PMID 22988594 .
  2. ↑ K. Ishii, I. Norota, Y. Obara: Endocytic regulation of voltage-dependent potassium channels in the heart. In: Journal of Pharmacological Sciences . Volume 120, Number 4, 2012, pp. 264-269, ISSN  1347-8648 . PMID 23165803 . PDF .
  3. ↑ Chen-Syuan Huang, Guan-Hsun Wang, Chun-Hwei Tai, Chun-Chang Hu, Ya-Chin Yang: Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K + channels in parkinsonian discharges . In: Science Advances . tape 3 , no. 5 , May 1, 2017, ISSN  2375-2548 , p. e1602272 , doi : 10.1126 / sciadv.1602272 , PMID 28508055 , PMC 5425237 (free full text) - ( sciencemag.org [accessed November 14, 2018]).
  4. ↑ JC Hancox, AF James: Refining insights into high-affinity drug binding to the human ether-à-go-go-related gene potassium channel. In: Molecular Pharmacology . Volume 73, Number 6, June 2008, pp. 1592-1595, ISSN  1521-0111 . doi : 10.1124 / mol.108.047563 . PMID 18381562 .
  5. ↑ J. Jehle, PA Schweizer, HA Katus, D. Thomas: Novel roles for hERG K (+) channels in cell proliferation and apoptosis. In: Cell death & disease. Volume 2, 2011, p. E193, ISSN  2041-4889 . doi : 10.1038 / cddis.2011.77 . PMID 21850047 . PMC 3181422 (free full text).